To investigate the histogenesis of lymphomatoid papulosis (LYP), we have analyzed the configuration of the beta, gamma, and delta T-cell receptor (TCR) and Ig genes in DNA from 31 biopsies of 18 patients with this condition and also from peripheral blood mononuclear cells of eight of these patients. Immunoglobulin genes were in a germ-line configuration in all patients, and TCR genes were in a germ-line configuration in six patients. In nine patients, one or two rearranged bands (RB) were detected with both beta and gamma TCR probes and in one patient with beta, gamma, and delta TCR probes. Two patients, in whom beta and delta TCR genes were in a germline configuration, had evidence of multiple discrete rearrangements of gamma TCR genes, consistent with a polyclonal T-cell population. Analysis of multiple biopsies revealed that RB, when present, were identical in different lesions from individual patients. All but one of the peripheral blood samples showed a germ-line configuration. The exception had evidence of a rearrangement of gamma and delta in peripheral blood and a beta and gamma rearrangement within tissue. This study has established that only a proportion of patients with LYP have a monoclonal T-cell proliferation. Correlation with the clinicopathologic and immunophenotypic data revealed that a T-cell clone was limited to patients with Willemze type B LYP or "mixed type" LYP, whereas patients with type A LYP consistently showed a germline configuration of TCR genes. This study indicates that in LYP the atypical hyperchromatic cerebriform mononuclear cells of type B invariably constitute a monoclonal T-cell population whereas the atypical CD30 positive type A cells represent a proliferation of cells of non-B, non-T-cell lineage.