The midbrain periaqueductal gray (PAG) is now recognized as a critical structure for the initiation and regulation of aggressive behavior in the cat. The PAG is also known to be rich in gamma-aminobutyric acid (GABA) receptors. In the present study, we sought to examine the possible role of this putative neurotransmitter in the modulation of affective defense and quiet biting attack behavior elicited by electrical stimulation of the PAG. Cannula-electrodes were employed for electrical stimulation as well as for microinjections of a GABA agonist (muscimol: 3, 12 and 22 pmol/0.25 microliters) and GABA antagonist (bicuculline: 22 and 68 pmol/0.25 microliters). After establishing predrug response threshold values for affective defense and quiet biting attack, these drugs were microinjected into the PAG sites from which these responses were elicited. Microinjections of muscimol (12 and 22 pmol) significantly suppressed the affective defense response in a dose- and time-dependent manner. Pretreatment with bicuculline (68 pmol) blocked the suppressive effects of muscimol (12 pmol) upon affective defense behavior. In contrast, this dose of muscimol failed to alter the response threshold for quiet biting attack behavior. Microinjections of vehicle alone (0.25 microliter of saline, pH = 7.4) did not modify the thresholds for either of these responses. These results indicate that, at the level of the PAG, GABA-ergic mechanisms are selectively involved in the regulation of affective defense behavior in the cat.