The effects of constant darkness, chronic lithium, clorgyline, imipramine and fluphenazine treatment on the content and diurnal rhythm of alpha-MSH in rat forebrain were investigated. The persistence of the alpha-MSH rhythm in constant darkness demonstrated that the rhythm was circadian in nature. Constant darkness increased the 24 h mean alpha-MSH concentration in brain while lithium, fluphenazine and imipramine decreased it. In addition, imipramine and clorgyline delayed the phase of the alpha-MSH circadian rhythm while lithium advanced it.