Spontaneous activity in bladder muscle strips from man, pig and rabbit has been compared using an in vitro superfusion technique. Field stimulation was used to study nerve-mediated activity. Bladder muscle strips from all areas of the rabbit bladder displayed rhythmic spontaneous activity. Spontaneous activity was regularly present in strips from the trigone region in man and pig, but was present in only 18 and 19% respectively of strips from the dome of the bladder. Strength-duration curves in the presence of tetrodotoxin (10(-7) g/ml) were constructed. The 'chronaxie' of the muscle was found to be considerably shorter than that of other smooth muscles, ranging from 6.1 ms in the rabbit to 12.9 ms in man. Frequency-response curves were constructed using trains of stimuli. The responses were not antagonized by hexamethonium (10(-4) M), but were markedly inhibited by tetrodotoxin (10(-7) g/ml), indicating that the responses were mediated by excitation of post-ganglionic nerves. Physostigmine (10(-7)-5 X 10(-6) M) produced a dose-related increase in the contractile response to field stimulation in all three species. Atropine (10(-8)-10(-6) M) produced an inhibition of the contractile response, but the maximum degree of inhibition differed considerably between the species. In the rabbit, 58% of the control response was attained, whilst in the pig this was only 22%. Atropine completely abolished nerve-mediated contractions in human bladder muscle. Phentolmaine (10(-7)-2.5 X 10(-7) M) had no significant effect on the frequency-response curve in any of the three species, and did not depress the atropine-resistant component in rabbit and pig. It is concluded that nerve-mediated activity in human bladder muscle is exclusively cholinergic, in contrast to most other mammals studied in which there is a significant non-cholinergic component. The finding of a shorter chronaxie in bladder muscle than in other smooth muscles suggests important differences in its physiological properties that merit further investigation.