Neuropsychological findings support a hypothesized relationship between obsessive-compulsive disorder (OCD) and the frontal lobe. The aim of the present study was to compare findings of neuropsychological tests of frontal lobe function in 28 OCD patients and 29 patients with major depressive disorder (MDD), all diagnosed according to DSM III-R criteria. The patient groups were homogeneous for educational level, handedness, duration of illness, and sex distribution. All 57 subjects received a battery of tests sensitive to frontal lobe dysfunction as well as the Wechsler Memory Scale (WMS). Clinical symptomatology in the MDD and OCD groups was assessed with the Hamilton Rating Scale for Depression and the Yale-Brown Obsessive-Compulsive Scale, respectively. The only significant difference between the two diagnostic groups for any of the neuropsychological indices, with age as a covariate, was in the Object Alternation Test, in which OCD patients had a significantly higher number of perseverative responses. Test performances were not correlated with clinical symptomatology or severity of illness. Our preliminary results confirm the hypothesis that there is a selective impairment of orbito-frontal cortex in OCD and seem to exclude the existence of specific frontal lobe dysfunction in MDD, even though the two disorders show clinical similarities.