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Twenty patients with steroid-insensitive glomerulonephritis were treated with azathioprine and prednisone in sustained low dosages. Serial parameters were measured to (1) assess functional response; (2) define any relationship between improvement in renal function and changes in the immune apparatus; (3) define criteria for patient selection; and (4) identify useful parameters to gauge therapeutic progress. Three patients had a complete remission, ten a partial remission, three slight improvement, and four continued to show deterioration despite treatment. Only one patient had septic complications. Functional response did not correlate with the degree of humoral or cellular immunosuppression. Azathioprine initially depressed immunoglobulin G (IgG) levels but after six months of therapy the levels of all immunoglobulins exceeded baseline values by nearly 50 per cent. Cellular immunity was never suppressed completely. Immunosuppression of humoral autoantibodies did not correlate with functional response. Renal histology, hyperalpha 2 -globulinemia and hypocomplementemia were the most reliable parameters in judging selection and probability of response in a patient with lupus glomerulonephritis. With other forms of glomerulonephritis, histopathologic criteria are not as well established and less useful. Hypocomplementemia and hyperalpha 2 -globulinemia, in the face of steroid unresponsiveness, were considered to be indications for antimetabolite therapy.