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Clinicopathologic correlations were explored in 79 patients at high risk for human immunodeficiency virus (HIV) infection who had lymph node biopsy for persistent lymphadenopathies and were followed for intervals of up to 7.2 years. Three histologic patterns, follicular hyperplasia with cytolysis (A), follicular involution with hypervascularity (C), and a combination of the previous two (B), were recognized. Ninety lymph node biopsies (79 primary and 11 sequential) were classified into the three histologic patterns and the results correlated with the immunologic data and clinical course. Of 31 patients who showed a pattern A at the initial biopsy, the condition of 58% remained stationary and 42% progressed to acquired immune deficiency syndrome (AIDS); of 31 patients who had initial B pattern, the condition of 36% remained stationary and 64% progressed to AIDS; and of 17 patients who initially had histologic pattern C, the condition of 6% remained stationary and 94% progressed to AIDS. Forty-one patients died during this follow-up, representing 32% of those who had a pattern A, 52% of those who had a pattern B, and 88% of those who had a pattern C at the initial lymph node biopsy. Medial survival times were 54.4 months for pattern A, 35.6 months for pattern B, and 8.4 months for pattern C. Sequential biopsies showed persistence of the same pattern or changes generally in the direction of pattern A to pattern C over variable amounts of time. Lymphocyte evaluation expressed by total counts of T4 cells, T8 cells, T4/T8 cell ratios, and anti-lymphocyte antibody levels expressed by increases in counts of surface immunoglobulin-positive lymphocytes showed positive correlations with lymph node histologic patterns. All three parameters proved to be useful prognostic indicators for the course of the HIV infection. The pathogenetic significance of lymph node histologic patterns, although not clearly understood, suggests the relation of follicular hyperplasia (pattern A) to acute viral lymphadenitis and of follicular involution with hypervascularity (pattern C) to cellular immune deficiency.