The effects of electrical stimulation and microinjection of morphine into the periaqueductal gray (PAG) on the 5-hydroxyindole oxidation current (280-300 mV) in laminae I-VI (800-2500 microns) of the spinal cord were examined using in vivo voltammetry in anesthetized cats. 2. Electrical stimulation of the PAG (PAG-S) both enhanced and attenuated the current. PAG-S increased the signal by 13.3 +/- 3.7% (laminae I-II: 800-1200 microns) or 19.0 +/- 3.6% (laminae V-VI: 1700-2500 microns) in comparison to control values. Attenuation by PAG-S decreased the signal by 15.3 +/- 2.6% (laminae I-II) or 13.3 +/- 2.0% (laminae V-VI) of control values. Naloxone antagonized signal enhancement by PAG-S. 3. Morphine (10 micrograms/microliter) microinjected into the PAG significantly increased the height of the signal (laminae I-II: 15.0 +/- 3.4%, laminae V-VI: 12.2 +/- 1.5%). Enhancement by microinjected morphine was antagonized by naloxone. In contrast, microinjected morphine also significantly decreased the signal by 10.4 +/- 2.7% (laminae I-II) and by 10.3 +/- 1.3% (laminae V-VI) of control values. 4. Microinjection of morphine and electrical stimulation of the PAG was observed both to enhance and attenuate the oxidation current of 5-hydroxyindole in the superficial and deeper dorsal horn. PAG may function to regulate the RVM-spinal serotonergic pathway, which modulates the transmission of nociceptive messages at the spinal cord.