The association between anxiety, depression, and lateralization of an epileptogenic focus was explored in 18 adult patients with a left temporal lobe focus, 21 with a right focus, 20 with bilateral temporal foci, and 16 individuals with absence seizures. No significant difference in the level of anxiety was found among the groups. However, patients with left-sided temporal lobe epilepsy scored significantly higher than other groups on self-ratings for depression. This could not be accounted for by factors such as duration of epilepsy, employment status, education, age at seizure onset, or medication status. The left temporal lobe epilepsy group had a nonsignificantly larger number of males and left-handed subjects. The possible interactions between gender, handedness, seizure focus, and vulnerability to depression are described.