In the isolated perfused guinea-pig heart low-pH buffer (pH 5), lactic acid (5 mM), capsaicin (10(-7) M) and nicotine (10(-4) M) all evoked a clear-cut release of calcitonin gene-related peptide (CGRP) from sensory nerves. Incubation with the proposed capsaicin receptor antagonist, capsazepine (10(-5) M), significantly reduced the CGRP release evoked not only by capsaicin but also by low pH and lactic acid, indicating a common mechanism of C-fibre activation, while the nicotine response remained unchanged.