In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. Thewv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion ofwv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum ofwv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of thewv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of thewv/wv striatum compared to +/+. [3H] Citalopram binding in thewv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within thewv/wv striatum, [3H] mazindol binding was almost completely absent (88–89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of thewv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers.