The ability of dopamine autoreceptor agonists to suppress the in vivo release or metabolism of dopamine in mouse brain was determined by measuring steady state levels of 3-methoxytyramine (3-MT) or dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), respectively. These experiments provide the first neurochemical evidence for dopamine autoreceptors in the mouse. (-)N-n-propylnorapomorphine, apomorphine, (+)-3-PPP, TL-99, and the novel dopamine autoreceptor agonist CGS 15855A each decreased 3-MT levels at doses that approximated their potency in the gamma-butyrolactone model. CGS 15855A suppressed dopamine release and metabolism to the same extent in the rat and mouse neostriatum. Generally, agonist-induced decreases in 3-MT levels were obtained to a greater extent or with lower doses than were changes in DOPAC or HVA. The autoreceptor efficacy of CGS 15855A was confined to the (+) and not the (-) optical isomer. Consecutive injections of CGS 15855A did not induce an acute tolerance to its actions but instead prolonged for at least 3.5 h the suppression of dopamine metabolism and release. The release and metabolism of dopamine in mouse limbic and striatal regions is regulated by autoreceptors with a pharmacological specificity that is similar to autoreceptors of the rat.