We compared the cognitive effects of randomly prescribed phenytoin (PHT) and carbamazepine (CBZ) therapy on newly diagnosed patients with epilepsy in a 2-year parallel group follow-up study. Fifteen patients were receiving PHT and 16 were receiving CBZ. Neuropsychological assessments were conducted before the treatment and after 6 and 24 months of steady-state drug therapy. Differential effects of PHT and CBZ during follow-up were observed in 3 of 32 measurements. PHT appeared to have negative effects on visually guided motor speed of both hands. In addition, the performance of the PHT group as compared with the CBZ group developed less positively in one visual memory task. The development of mood as measured by Profile of Mood States (POMS), was quite similar in both drug groups; Tension, Depression, and Bewilderment decreased and Vigor increased during the follow-up. The results suggest that the long-term effects of PHT as compared with those of CBZ on cognition are few and restricted mainly to some visually guided motor functions. The effects of PHT on cerebellar function as a possible mechanism for these changes is discussed.