The relationship between performance on information processing efficiency measures and MRI-derived lesion volume including global and regional T2 and T1 lesion volumes was investigated in 20 patients with relapsing–remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Processing speed, as measured by the Sternberg Memory Scanning Test, was significantly correlated with posterior fossa lesion volume and slowed reaction time in seven out of eight patients (six out of seven with SPMS) with any lesion volume in the posterior fossa suggesting a ‘threshold effect’. Processing capacity as measured by the Salthouse Keeping Track Test was not significantly correlated with the MRI measures. Cognitive performance did not correlate with Expanded Disability Status Scale score, depression or fatigue, and patients performed within normal limits on tests of attention/concentration ability. The significant relationship between posterior fossa lesion volume and memory scanning speed in this study suggests that pathological damage in the posterior fossa may contribute to slowed cognitive processing and may be an important direction for future studies of cognitive function in multiple sclerosis. Lack of correlation of cognitive measures with the other MRI measures may be due to low lesion volume relative to other studies, sample composition, and limited pathological specificity of the MRI measures.