1. Isolated papillary muscles from guinea-pig hearts were paced at a constant frequency and isometric contractions reported. 2. Guinea-pigs were either untreated or pretreated with reserpine. Three pretreatment schedules were used; a) 0.5 mg kg-1 i.p. at 24 h, b) 5.0 mg kg-1 at 72 h and 3.0 mg kg-1 at 48 and 24 h, or c) 0.1 mg kg-1 daily for 7 days. 3. Cumulative concentration-response curves for the isoprenaline-induced increases in tension were obtained. The geometric mean EC50 values after the 3 and 7 day reserpine pretreatment schedules were significantly (P less than 0.05) less than for untreated guinea-pigs indicating a supersensitivity. 4. EC50 values for the positive inotropic responses to histamine and calcium in papillary muscles from reserpine-pretreated guinea-pigs did not differ significantly (P less than 0.05) from those from untreated animals. This suggests that the supersensitivity to isoprenaline is beta-adrenoceptor specific. 5. Membrane fractions were prepared from the ventricles of the untreated and reserpine-pretreated guinea-pigs from which papillary muscles had been removed. Binding of [3H]-dihydroalprenolol ([3H]-DHA) to beta-adrenoceptors of these membranes was determined. Equilibrium dissociation constants (KD) and total numbers of binding sites (Bmax) were determined by Scatchard analysis of the saturation curves for [3H]-DHA binding. 6. There was no increase in affinity (fall in KD value) or change in the total number of binding sites associated with reserpine-induced supersensitivity. The equilibrium inhibition constant (Ki) for the displacement of [3H]-DHA binding by isoprenaline was also identical in membranes from untreated and reserpine-pretreated animals. Thus reserpine-induced supersensitivity to isoprenaline does not appear to involve a change in affinity for the beta-adrenoceptor or in receptor numbers as determined by [3H]-DHA binding.