This study examined relations of mesiotemporal lobe tissue volumes with neuropsychological (NP) functions in a sample of patients with first episode schizophrenia. Three contiguous compartments of the mesiotemporal lobe were measured on magnetic resonance images, comprising primarily amygdaloid, anterior hippocampal, and posterior hippocampal tissue volumes. NP measures were derived from a comprehensive battery. Decreased volume selectively in the anterior hippocampal formation was associated with lower scores on measures of executive and motor functions usually considered sensitive to the integrity of frontal lobe systems. Measures of other NP functions, and global intellectual ability, were not related to mesiotemporal volumes. The findings that morphologic abnormalities in the mesiotemporal lobe are associated with impairment of frontal lobe functions point to a defect in an integrated functional system that includes both frontal and mesiotemporal components. The findings are consistent with the hypothesis that neurodevelopmental defects affecting the morphology of the anterior hippocampal formation may be manifest later in life as impairments in fronto-limbic control. </p>.