We performed histologic and selected histochemical and immunohistochemical studies on rheumatoid nodules (RN) from 12 patients and lesions of subcutaneous granuloma annulare (SGA) from nine patients. The mean age for patients with RN was 56 years, while that for SGA patients was 19 years. In contrast to those with RN, none of the patients with SGA had arthritis. RN tended to show homogeneous, eosinophilic necrobiosis, giant cells within palisaded foci, and significant stromal fibrosis; while lesions of SGA showed pale, edematous necrobiosis, an absence of giant cells, and lesser degrees of fibrosis. The single most helpful histochemical method was alcian blue, which stained necrobiotic foci in all cases of SGA but in only one case of RN. Epithelioid cells in both disorders stained positively for muramidase. IgM was found in vessel walls in two cases of RN. While the mechanisms of these disorders are not entirely clear, it appears that RN can usually be reliably distinguished from SGA on histologic grounds alone.