As part of a wide ranging study investigating the prevalence, demographic and disease related characteristics of pathological laughing and crying (PLC) in multiple sclerosis (MS), a putative role for the prefrontal cortex was also explored. Eleven multiple sclerosis (MS) patients with carefully defined PLC were compared to a control group of 13 MS patients without PLC on various cognitive indices known to be sensitive to frontal lobe dysfunction. Although the two groups did not differ with respect to age, sex, physical disability, disease course, duration of MS, years of education, premorbid IQ, and depression, the PLC group performed more poorly on the Stroop test and a measure of verbal fluency. They also showed a trend to make more total errors on the Wisconsin Card Sort Test. The relevance of these findings to the pathogenesis of PLC is discussed, in particular whether the syndrome is, in part, mediated by dysfunction of the prefrontal cortex.