Electrophysiological and biochemical techniques were used to study midbrain dopamine systems. In the electrophysiological studies, projection areas of individual dopaminergic cells were identified by antidromic activation. Dopamine cells which innervate the piriform cortex and those that innervate the caudate nucleus demonstrated their usual dose-dependent inhibitory response to both the intravenous administration of the direct-acting dopamine agonist apomorphine and the microiontophoretic application of dopamine. In contrast, the firing rate of dopamine neurons which project to the prefrontal cortex and of those terminating in the cingulate cortex was not altered by either the intravenous administration of low to moderate doses of apomorphine or microiontophoretically applied dopamine. The mean basal discharge rate and degree of burst firing was also different between these subgroups of midbrain dopaminergic neurons. Mesoprefrontal and mesocingulate dopamine neurons had mean firing rates of 9.3 and 5.9 spikes/s respectively, and showed intense burst activity. Mesopiriform and nigrostriatal dopamine cells had discharge rates of 4.3 and 3.1 spikes/s and displayed only moderate bursting. The dopaminergic nature of those mesocortical neurons insensitive to apomorphine and dopamine was confirmed using combined intracellular recording and catecholamine histofluorescence techniques. Thus, after the intracellular injection of colchicine and subsequent processing for glyoxylic acid-induced histofluorescence, the injected cells could be identified by their brighter fluorescences compared to the surrounding, normally fluorescing, non-injected dopamine neurons. Using biochemical techniques, subgroups of midbrain dopaminergic systems were again found to differ. The administration of gamma-butyrolactone increased dopamine levels in all areas sampled (prefrontal, cingulate and piriform cortices as well as the caudate nucleus). However, although this effect was readily reversed in both the piriform cortex and caudate nucleus by pretreatment with apomorphine, this treatment had no effect on the increased dopamine levels observed in the prefrontal and cingulate cortices. In addition, the decline in dopamine levels after synthesis inhibition with alpha-methyltyrosine was significantly faster in the prefrontal and cingulate cortices relative to the caudate nucleus. The piriform cortex showed an intermediate decline which was not significantly different from that observed in any of the other regions.(ABSTRACT TRUNCATED AT 400 WORDS)