Using unfixed rat liver sections as substrate for the detection of antinuclear antibodies, distinct nuclear staining was observed in the sera of patients with systemic sclerosis. Its reaction differed from previously described fluorescence patterns and was characterized by numerous fine speckles throughout the nucleus associated with one or more coarse lines. These lines were more evident in diluted sera, when fine speckled fluorescence faded. This picture "fine speckles with lines" (FLS) was defined. The FLS pattern was present in 35% of 91 patients with systemic sclerosis, while it was absent in 517 patients with rheumatic and non-rheumatic disorders and in 100 matched healthy subjects. Moreover, the FSL pattern was significantly associated with the diffuse subset of systemic sclerosis (50% of cases) and was related to the presence of anti-Scl-70 antibody. These results indicate that this fluorescent pattern of antinuclear antibodies may be considered a simple and very useful aid in the diagnosis and prognosis of systemic sclerosis.