Expression of the bcl-2 protein and bcl-2 mRNA at the individual cell level was semiquantitatively examined in normal quiescent peripheral blood lymphocytes and pokeweed mitogen- or concanavalin A and interleukin-2-induced lymphoblasts in vitro by microscopic fluorometry using immunofluorescence and fluorescein-labeled in situ hybridization. Approximately 90% of normal quiescent T and B lymphocytes expressed bcl-2 protein at a level which was compatible with that of bcl-2 mRNA. On the contrary, most mitogen-induced lymphoblasts showed a posttranscriptional suppression of bcl-2 protein expression. However, bcl-2 protein was not downregulated by the posttranscriptional suppression in all lymphocytes activated in vitro, but approximately 15% of the lymphoblasts still expressed bcl-2 protein at a higher level than nontransformed quiescent small lymphocytes; thus bcl-2 protein expression in lymphoblasts showed a distinct bimodal pattern. Furthermore, it was supposed that lymphoblasts with no detectable bcl-2 protein might fall into apoptosis but the remainder, expressing high levels of bcl-2 protein, could escape apoptosis. Thus, the bcl-2 gene may play an important role as a regulator of apoptosis in the human immune system.