Twice daily topical administration of echothiophate for 2 weeks to the eyes of living cynomolgus monkeys produced profound subsensitivity of the accommodative response to pilocarpine and an approximately 50% decrease in the number of specific binding sites for 3H-quinuclidinyl benzilate (3H-QNB) in the ciliary muscle without a change in their affinity. When echothiophate treatment was discontinued, functional cholinergic sensitivity and the number of QNB binding sites both returned to normal over a similar 4-8 week period. Most animals had a modest overshoot of both functional sensitivity and number of binding sites for at least several weeks thereafter. The treated to control eye ratios for the number of binding sites and accommodative response to pilocarpine were correlated and the plot of log treated to control binding site ratio versus treated to control accommodation ratio resembled a dose-response curve. Similarly, the treated versus control eye differences for the two parameters were correlated, with the regression line passing through the 0-0 axis intercept. Collectively, these findings suggest that agonist-induced modulation of functional cholinergic sensitivity in the parasympathetically innervated (as opposed to denervated) ciliary muscle occurs by a muscarinic receptor-mediated mechanism. This system appears to provide a useful model to study the regulation of ciliary muscle cholinergic sensitivity.