The effect of kainic acid (KA)-induced lesions of retinal neurons on regulation of serotonin N-acetyltransferase (NAT) activity in chicken retina was investigated. Although NAT activity was higher in KA-lesioned retinas than in controls, the pattern of diurnal variation of enzyme activity throughout 36 h of constant darkness was similar for both tissues. Quinpirole, a selective D2-dopamine receptor agonist, inhibited the nocturnal increase of NAT activity in both control and KA-treated retinas. Quinpirole was significantly more potent in KA-treated retinas than in controls; the ED50 value for quinpirole was 3 times lower in KA-treated retinas than in control tissues. KA treatment markedly reduced retinal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). We conclude that: (1) NAT activity in retina is localized primarily to KA-insensitive cells, presumably photoreceptors; (2) KA-sensitive inner retinal neurons are not essential to the maintenance of the circadian rhythm of NAT activity; and (3) KA-induced lesions of retinal cells result in supersensitivity of D2-dopamine receptors regulating NAT activity in a mechanism that involves adaptive changes following a decline in retinal dopamine neurotransmission.