HIV preferentially infects the RO+ memory subset of CD4+ lymphocytes, and these cells are lost earlier in HIV infection than their RA+ counterparts. Although both populations express similar amounts of CD4 and bind the HIV envelope glycoprotein (gp120) equally well, calcium signals and CD4 down-regulation subsequent to gp120 binding are not the same in both populations. Data suggest these disparities are mediated by differential tyrosine kinase (TK) regulation. Syncytium formation is enhanced in RO+ cells, partly a consequence of increased leucocyte function antigen-1 (LFA-1) expression and, again, partly due to altered TK regulation. After in vitro HIV infection, reverse transcription is not detected in RA+ cells, is minimal in the RO+ class II- population, but progresses well in RO+ class II+. Infection followed by mitogen stimulation permits reverse transcription in all cells. HIV infection of RO+ cells is enhanced moderately at multiple points in the virus life cycle.