Previous studies of immunosuppressive therapy in asthma have been uncontrolled and conflicting in their results. Two double-blind controlled cross-over trials using two dosage levels of azathioprine (2 mg/kg and 5 mg/kg for three and four weeks respectively) in a total of 20 patients with chronic severe asthma are described. Both objective and subjective assessments by independent observers indicated no significant change in the groups as a whole. However, in four patients, an improvement was attributed to azathioprine therapy. Two patients in whom sputum production was copious showed marked clinical improvement and reduced sputum volume. In four patients, exacerbations of asthma occurred within two weeks of starting azathioprine and a causal relationship was suspected. No serious depression of circulating white blood cells occurred in any patient.