The human class II-associated chondroitin sulfate proteoglycan (CSPG) was originally detected as an approximately 40-70 kd species from normal human tonsil cells and Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines. The identification of the invariant chain as the core protein of the CSPG allowed us to directly assay for the CSPG on both class II positive and negative immunocompetent cells of other lineages. Our results indicate that the CSPG is present on the class II-positive monocyte-like cell line U937 and T-cell line HUT-102, but not on the class-II negative T-cell line CCRF/CEM. No class II positive cells were found that did not also express the CSPG. The expression of the CSPG on U937 cells is increased after stimulation with gamma-interferon and PMA, paralleling the previously described increase in class II and invariant chain expression. In addition, the CSPGs from U937, HUT-102, and Raji, all cell lines derived from human malignancies, migrate as an approximately 55-90 kd species, larger than the CSPG previously characterized. However, the core proteins of the CSPG from all cells studied appear as two bands of 38 and 28 kd, indicating the size difference in the CSPG is attributable to differences in the glycosaminoglycan chains.