Topical echothiophate administration to the cynomolgus monkey eye for 5-6.5 months produced marked subsensitivity of the accommodative response to pilocarpine and a 65% decrease in specific high affinity 3H-QNB binding sites (ostensibly indicating muscarinic receptors) in the ciliary muscle. The decrease in 3H-QNB binding sites was quantitatively similar in surgically untouched, totally iridectomized, and ciliary muscle disinserted eyes. Following a 5-month off treatment recovery period, 3H-QNB binding sites increased to more than twice the number in untreated control eyes. In echothiophate-treated eyes whose contralateral eyes had previously received atropine+echothiophate, 3H-QNB binding sites were three to six times more numerous than in other long-term echothiophate-treated eyes, and one to two times more numerous than in untreated controls. Topical pilocarpine administration for 1 day to 7 months reduced ciliary muscle 3H-QNB binding sites by approximately 25%. Alterations in muscarinic receptors during and following cholinergic drug therapy may in part explain the observed subsensitization and recovery of ciliary muscle physiological responses.