The effect of swim stress on the in vivo binding of [3H]N-methylspiperone in the striatum of the mouse was investigated. Mice were forced to swim for 5 min at 18 degrees C and the time course of radioactivity in the striatum and cerebellum, following intravenous injection of [3H]N-methylspiperone was measured. The ratio of radioactivity in the striatum to that in the cerebellum was plotted as a function of time for the estimation of in vivo binding to dopamine D2 receptors. Immediately after the swim stress, a significant decrease in binding to D2 receptors in vivo was observed. Neither the KD nor Bmax determined by in vitro binding were altered by swim stress. The time course of the changes in binding, within a 24 hr period, following the swim stress was also studied and a rapid reversal of binding, within 1 hr after the swim stress was observed. In vivo binding of [3H]N-methylspiperone in the cerebral cortex, which appeared to involve serotonin receptors, as well as D2 receptors, was not significantly altered by the swim stress. A saturation study of in vivo binding indicated that the decreases in binding to D2 receptors, due to swim stress, were primarily caused by changes in the apparent affinity rather than in the number of binding sites available in vivo. These results support the hypothesis that micro-environmental factors, including the diffusion barrier to the synapse, might be altered by swim stress.