Primary or secondary progression in multiple sclerosis (MS) leads to irreversible disability. While neuronal and axonal loss are widely accepted to underlie progression, any axonal subtype selectivity remains equivocal, although human post-mortem studies indicate a selective loss of the smallest axons (e.g. Ganter et al. 1999; Evangelou et al. 2001). One common early symptom of MS is optic neuritis (ON) and we have studied the functional effects of induced ON in a transgenic mouse model, with an enhanced immune response to myelin oligodendrocyte glycoprotein (MOGTCR; Lidster et al 2013), in ex-vivo isolated optic nerve. To induce ON, mice were injected intraperitoneally with 150 ng Bordetella pertussis toxin on day 0 and day 2, and on day 14 with 0.25 mg MOG-specific Z12 mouse IgG2a monoclonal antibody. All procedures were approved by the UK Home Office and the local ethics committee. Supramaximal compound action potentials were recorded that normally comprise more than one component, the slowest component interpreted as the functional correlate of the smallest axons. We analyzed the shape of the action potential, expressing the amplitude of the slowest component as a fraction of the peak (Fig. 1).Our data indicate a downward trend in the average slow component amplitude (Fig. 1A), and over the same period a statistically-significant disappearance of the slow component (Fig. 1B), p = 0.0184,(n = 19, 5; day 0 + day 7, day 21, respectively; Fisher exact test), supporting the hypothesis that in ON, functional loss is likely to be greatest in the population of smallest axons.