The minimal inhibiting concentrations (MIC) of ampicillin, trisulfapyrimidines, and various combinations of these drugs were determined for four clinical isolates of Nocardia asteroides on Mueller-Hinton agar. The combination of ampicillin and sulfonamides was found to be synergistic for three of the four isolates when an inoculum of 10(3) to 10(4) organisms per ml was used. (Synergism was defined as occurring when the MIC of each of the drugs in combination was one-quarter or less of the MIC of each drug alone.) All four isolates were inhibited by concentrations of the drugs in combination that were clinically achievable. Combined therapy with ampicillin and sulfonamides was used in four immunologically suppressed renal transplant patients who had pulmonary infection with N. asteroides. Clinical improvement was noted within 2 weeks in all patients, and the pulmonary infiltrates cleared by 6 months in three patients. One patient died from an unrelated illness 10 days after starting therapy. The disease was arrested in two patients who were maintained on full immunosuppressive therapy.