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A systemic lupus erythematosus-like syndrome developed simultaneously with pulmonary reactions of the chronic type in three female patients after treatment with nitrofurantoin for 12, 27 and 38 months, respectively. The syndrome was characterized by elevated ESR, polyclonal hypergammaglobulinaemia, the presence of IgG antinuclear antibodies and a positive latex-fixation test. Two patients had severe arthralgia and one of them peripheral lymphadenopathy. Pleural effusion and a chronic active hepatitis were present in the third patient, in whom interstitial cystitis also developed. All signs and symptoms of the lupus-like syndrome disappeared, without corticosteroid or other medication, when nitrofurantoin was omitted. The diminution of pulmonary infiltrates and the reversal of interstitial cystitis also appeared to be directly related to cessation of nitrofurantoin therapy. Our findings indicate that long-term medication with nitrofurantoin may cause, in addition to pulmonary changes, a simultaneous lupus-like syndrome our data also raise the possibility that interstitial cystitis may occur as an adverse reaction to nitrofurantoin therapy.