The L-arginine-nitric oxide (NO) pathway plays a significant role in the physiopathology of chronic renal failure (CRF)^1,2. Malnutrition, a common feature in CRF, adversely affects both uraemic patient morbidity and mortality₃. L-arginine is a cationic amino acid, precursor for NO synthesis. We have previously demonstrated that the transport of L-arginine in platelets is increased in well-nourished CRF patients. In the present study, we have investigated in uraemic platelets, the correlation of NO synthesis, NO-synthase activity and L-arginine and nutritional status. A total of 17 uraemic patients on haemodialysis were included in the study. NO synthase (NOS) activity, cGMP and amino acid profiles in plasma were analyzed in malnourished and well-nourished patients. Basal NOS activity (pmol/108cells) in platelets, determined from the conversion of L-[³H]-arginine to L-[³H]-citrulline (pmol/10⁸cells), was increased in well-nourished (0.38 ± 0.14) compared to malnourished patients (0.09 ± 0.02) and controls (0.17 ± 0.008). GMPc content (ELISA Kit, pmol/108cells) was also enhanced in platelets from well-nourished (0.64 ± 0.15) compared with controls (0.21 ± 0.09) and malnourished patients (0.18 ± 0.04). Plasma L-arginine concentration (μM) was significantly reduced in malnourished CRF patients (54 ± 14) and well-nourished CRF patients (86 ± 9) compared to controls (125 ± 5). Our results demonstrate that in malnourished uraemic patients, not only plasma L-arginine is reduced but their platelets lack the up-regulation of NO-synthase activity and NO synthesis present in well-nourished patients. A possible mechanism behind the reduction in the activity of the L-arginine-NO pathway in platelets from malnourished patients may be a diminished L-arginine transport. A limited L-arginine availability could be the explanation for the observed increased incidence of cardiovascular events in CRF patients with malnutrition.