Antinuclear antibodies (ANA) were studied in 122 patients with cryptogenic fibrosing alveolitis (CFA) and compared with age- and sex-matched control subjects. Fluorescent ANA were detected in 32% of the patients and showed a correlation with the presence of a systemic connective tissue disease; ANA were present in 6% of the control subjects, 21% of the patients with CFA alone, and 46% of those with CFA and an associated connective tissue disease. Antibodies to the defined nuclear antigens: deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), the Sm antigen, and Sjögren's syndrome A and B antigens (SS-A and SS-B) were examined to establish whether their presence was diagnostic of the associated diseases. Antibodies to DNA and Sm antigens identified 3 patients with CFA and systemic lupus erythematosus. The frequency of antibodies to SS-A and SS-B did not differ from that in control subjects. Antibodies to nRNP, detected in 15 (12%) of the patients (at a high titer in 5), were associated with females, the presence of Raynaud's phenomenon, and rheumatoid factor in the serum. However, despite the detection of these antibodies, none of these patients met fully the proposed criteria for the diagnosis of mixed connective tissue disease.