Blood pressure (BP) and heart rate (HR) in endothelin-3 (ET-3) null (-/-) knockout mice and ET(A) receptor (-/-) mice were measured using the servo null pressure measuring technique under halothane anaesthesia. In infant ET-3 (-/-) mice (2-3 weeks old), mean BP and HR were 55+/-2 mmHg and 436+/-30 beats/min respectively. These values were not different from those in age-matched wild-type mice (53+/-3 mmHg and 430+/-18 beats/min respectively). Baroreflex sensitivity, which was calculated as the slope of the relationship between systolic BP and RR interval on an ECG, was also similar in ET-3 (-/-) mice (0.84+/-0.20 ms/mmHg) and wild-type mice (1.07+/-0.38 ms/mmHg). ET(A) receptor (-/-) mice were obtained by caesarean section on the expected day of delivery and tracheotomized, so that they would live for more than 24 h. Mean BP and HR in ET(A) receptor (-/-) mice were 15+/-1 mmHg and 333+/-6 beats/min respectively. These values were not different from those in age-matched, similarly treated wild-type mice (16+/-3 mmHg and 308+/-10 beats/min respectively). Baroreflex sensitivity in the newborn ET(A) receptor (-/-) mice (0.45+/-0.15 ms/mmHg) and wild-type mice (0.31+/-0.06 ms/mmHg) were very low compared with the values in infant wild-type mice, but not different between the mutant mice and their littermates. Moreover, HR in awake ET(A) receptor (-/-) mice (396+/-13 beats/min) was not different from that in wild-type mice (409+/-13 beats/min). These results show that the ET(A) receptor and ET-3 are not involved in cardiovascular regulation, at least during the very early life of the mice. A possible involvement of the ET(A) receptor in BP regulation, if any, seems to occur at later times and/or in some pathological settings.