Oct1 and Oct2 are transcription factors of the POU homeo-domain family that bind to the Ig gene octamer sites, regulating B-cell-specific genes. The function of these transcription factors is dependent on the activity of B-cell-restricted coactivators such as BOB.1/OBF.1. Independent studies of the expression of these proteins in non-Hodgkin's lymphoma have been restricted to single markers, and most lack data concerning immunohistochemical expression. Thus, we have investigated the expression of Oct1, Oct2, and BOB.1/OBF.1 in human reactive lymphoid tissue and in a series of 140 Hodgkin and non-Hodgkin's lymphomas. None of these proteins was found to be restricted to B cells, although only B cells expressed high levels of all three markers. Additionally, germinal center B cells showed stronger Oct2 and BOB.1/OBF.1 staining. Consequently, most B-cell lymphomas showed reactivity for all three antibodies. Oct2 expression was significantly higher in germinal center-derived lymphomas, although other B-cell lymphomas also displayed a high level of Oct2 expression. Although T-cell lymphomas and Hodgkin's lymphomas expressed some of these proteins, they commonly exhibited less reactivity than B-cell lymphomas. Despite not being entirely cell-specific, the strong nuclear expression of Oct2 and BOB.1/OBF.1 by germinal center- derived lymphomas makes these antibodies a potentially useful tool in lymphoma diagnosis.