Peroxisomes are involved in the synthesis and degradation of complex fatty acids {1). They contain enzyme pathways mostly analogous to those present in mitochondria for beta-oxidation as well as a specific pathway responsible for alpha-oxidation. An alternative omega-oxidation pathway for metabolism of fatty acids exists which involves both microsomes and peroxisomes. Biochemical defects in the assembly of peroxisomes can either have multiple biochemical effects if they affect the common PTS-1 signal domain used for protein import into the organelle or be more restricted in their phenotype if they affect the smaller number of enzymes imported through the PTS-2 system.Individual enzyme defects within the 60-200 proteins present in the peroxisome have also been characterised in many cases. The common spine for fatty acid metabolism in the peroxisome is the beta-oxidation pathway and it receives inputs at various points including from alpha-oxidation and also from racemisation of organic molecules including both fatty acids and bile acids(2). The chain length specificity of alpha-oxidation and maybe beta-oxidation is likely provided by the use of sterol carrier protein-2 which seems to act as a specific carrier molecule for these pathways (2). Short end-products are then exported through a carnitine-based transport pathway for further metabolism in the mitochondria. Clinically peroxisomal diseases are associated with neurological signs affecting the central nervous system (e.g. blindness, deafness, ataxia), the peripheral nerves (neuropathies) and defects in growth and development (intellectual impairment, chondrodysplasia and osteogenesis). One example of where the role of the different peroxisomal pathways has been clarified is Refsum disease- a defect in alpha-oxidation of phytanic acid derived from food sources. The adult-onset phenotype comprises blindness, anosmia and associated neurological symptoms whose presence and severity depends on both the length of exposure and plasma levels of phytanic acid. The clinical severity of the phenotype depends not only on environmental factors (e.g. dietary intake of phytanic acid) but also probably on the relative remaining activity of the alpha- and omega-oxidation pathways. Refsum disease is caused both by mutations in enzymes in the alpha-oxidation pathway and by defects in the PTS-2 signal driven import of these proteins (3). Different mutations in the Peroxin-7 carrier for proteins with PTS-2 signalling sequences give rise to a variety of phenotypes ranging from rhizomelic chondrodysplasia to Refsum disease. In many ways this is analogous to the mutations in the PTS-1 import pathway which give rise to phenotypes ranging from Zellweger disease to infantile Refsum disease but whose greater severity leads to clinical presentation at neonatal-childhood ages. All the mutations described to date in phytanoyl-coA hydroxylase, the principal enzyme affected in Refsum disease have been shown to be completely inactivate this 2-oxoglutarate-dependent oxygenase (4). While some mutations can be partially rescued in vitro with other chemical co-substrates as would be predicted from the alterations in the binding pocket, this approach has not yet been successful in vivo. A number of partial phenocopies of Refsum disease have been described through defects in enzymes further down the pathway including in alpha methyl-acyl CoA racemase though some remain still to be identified. Defective alpha-oxidation results in accumulation of phytanic acid that due to its structure cannot be beta-oxidised. The mechanism of phytanic acid neurotoxicity has recently been partially elucidated with the finding that it acts to inhibit complex I metabolism in the mitochondrion in a manner analogous to rotenone. An alternative variable capacity pathway for phytanic acid metabolism exists through omega-oxidation. The enzymes involved in this pathway have recently been characterised and include a microsomal P450 system cytochrome allied to peroxisomal beta-oxidation (5). This presentation will review the clinical-biochemical correlations of peroxisomal fatty acid metabolism and how these may be relevant to neurological disease.