Increases in minute ventilation (V'E) have been observed during exacerbations of asthma and in response to administration of histamine. However, it is not yet clear how the breathing pattern is affected, and whether the increase in V'E is found in general. In the present study, the effects of inhalation of histamine on respiratory frequency (fR), tidal volume (VT), V'E, and on functional residual capacity (FRC) were evaluated in 63 humans. Forty four subjects were hyperresponsive (BHR+). In each of these subjects, the doses of histamine applied for the present study (mean 3.5 mg x mL(-1)) caused a decrease in forced expiratory volume in one second (FEV1) that was greater than 20% of the control value. The dose of histamine applied in the 19 nonhyperresponsive subjects (BHR-) was substantially larger (8.0 mg x mL(-1)) whilst for this dose the decrease in FEV1 was less than 20% of control value. After histamine, fR was significantly increased in both subgroups of subjects, BHR+ and BHR-. The increase in V'E was significant in BHR- but not significant in BHR+. In general, the changes in V'E,fR and VT were not uniform; comparable numbers of subjects responded with increases (n=33) and decreases (n=30) in V'E. For fR 40 subjects responded with an increase and 23 with a decrease, and for VT these numbers were 26 and 37, respectively. The increase in FRC after histamine was significantly larger in BHR+ subjects than in BHR-. These findings may be interpreted to indicate that different mechanisms with opposite effects may be operating simultaneously, e.g. excitation of central inspiratory activity by stimulation of rapidly-adapting pulmonary stretch receptors, which will promote increases in respiratory frequency, tidal volume and minute ventilation, and bronchoconstriction with increased airway resistance, which will promote decreases in these parameters. As a consequence, depending on the net result of these opposite contributions to, e.g. minute ventilation, administration of histamine will cause an increase in minute ventilation in one subject and a decrease in another.