The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (PAG) were investigated in rats. Long-lasting depressor responses were elicited from 67 sites in the hypothalamus and ZI. Effects on HR were variable, except for the ZI where bradycardiac responses were evoked. The amplitude of the depressor responses was significantly correlated with baseline MBP on stimulation of the dorsomedial hypothalamic nucleus (DMH) or the dorsal hypothalamic area. Extracellular single-unit recordings were made from 94 PAG neurons. Most units were located in the ventral half of the PAG (62/94), where spontaneous firing rates were significantly higher than in the dorsal half: 12.5 +/- 1.4 spikes/s as compared to 6.0 +/- 0.9 spikes/s. Changes in PAG neuronal activity to both ipsi- and contralateral hypothalamic stimulation were observed. Most neurons were inhibited or unresponsive. There was no site specificity: responsive and unresponsive neurons were scattered throughout the PAG. Inhibition was most effectively evoked by stimulation of the DMH (25 out of 39 neurons) and the ZI (9 out of 15 neurons). In most neurons, the inhibition strictly followed the time course of hypothalamic stimulation. The results suggest that PAG as well as nonPAG pathways participate in the hypothalamic control of cardiovascular function.