Platelet-activating factor (PAF) has been shown to alter the trans-retinal potential recorded from light-stimulated isolated retina. In the present study, we investigated the effect of cholera and pertussis toxins on PAF-induced impairment of the electroretinogram (ERG). Administered alone, 2 x 10(-7) M PAF induced a very marked and rapid drop in the b-wave amplitude. When 75 micrograms/l of cholera toxin was coadministered with PAF in the perfusion solution, no b-wave drop was observed, suggesting that the effect of PAF on retinal function was mediated by GTP-binding protein (G protein). Similarly, a low dose of pertussis toxin (5 micrograms/l) was sufficient to antagonize the action of PAF on the ERG. Our results suggest that the irreversible and deleterious effect of PAF on ERG is mediated by a G protein mechanism, located in the neural retina.