To examine the possible usefulness of the immunomodulating antiinflammatory drug, hydroxychloroquine (HCQ), in the treatment of asthma, we studied the response of 11 asthmatics, four severe symptomatic nonsteroid dependent and seven steroid-dependent, in an open label 28 week trial at doses of 300 to 400 mg/d. Evaluation measures included daily symptom diary scores of six symptoms, subjective global evaluation, spirometric flow studies, and cumulative monthly steroid dosages. Baseline plasma theophylline and IgE levels were also obtained and compared with values during treatment. For the group as whole, mean FVC and FEV1 increased 10% and 17% respectively (P less than .01) and the mean of each of six symptom scores declined significantly (P less than .05). Among the nonsteroid-dependent asthmatics, the mean FVC and FEV1 rose 19% and 32% respectively (P less than .05) and mean symptom scores for five of six symptoms declined from baseline (P less than .05). Among the steroid-dependent patients, cumulative mean monthly steroid dosage required decreased 50% from 383 mg at entry to 191 mg at week 28 (P less than .01), mean FVC and FEV1 increased by 7% and 9%, although neither of these changes achieved significance, and two of six symptom scores improved (P less than .05). Comparison of pretreatment IgE levels to levels during treatment in ten patients demonstrated a fall from a mean of 645 to 339 IU/mL (P less than .05). Adverse reactions to HCQ were infrequent and did not require discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)