In a previous study from our laboratory (Akagi and Townley) we reported that basophils from asthmatic patients off medication show spontaneous histamine release (SHR) significantly higher than asthmatic patients on chronic medication. Both groups of asthmatics showed significantly higher SHR than normal subjects. These findings led us to test the in vitro effect of various therapeutic agents on SHR. Theophylline exerted the most pronounced inhibitory effect on SHR (P less than .005). The effects of isoproterenol and PGE1 were significant (P less than .005) but less than theophylline. These in vitro findings led us to evaluate the effect of a single dose, orally administered bronchodilator on in vitro SHR from asthmatic subjects. The effect of theophylline 250 mg and metaproterenol 20 mg on pulmonary function and SHR was evaluated on separate study days. Four of the eight asthmatic subjects showed greater than 10% SHR. The baseline value of SHR in the same individuals on two different study days showed significant correlation (r = .82). A single dose of metaproterenol or theophylline increased the pulmonary function but failed to influence the SHR. Although SHR occurs in asthmatic subjects, it is not influenced by single dose bronchodilation.