The proto-oncogenes have the capacity for conversion to an oncogene that is capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in the neoplastic transformation of B-cell malignancies, we have analyzed their expression in 18 fresh samples obtained from the peripheral blood of patients with a variety of B-cell malignancies. A high-molecular weight c-k-ras transcript (5.2 kb) was detected in all samples including normal lymphocytes. In contrast, a low-molecular weight c-k-ras transcript (1.2 kb) was not detected in our control normal lymphocytes, but was found in 9 fresh samples. The 1.2 kb c-k-ras transcript was expressed 2-3-fold higher than the 5.2 kb c-k-ras transcript. C-h-ras (2.9 kb, 1.4 kb) was expressed at a low level in 4 and 13 samples, but not in normal lymphocytes. C-myc (2.3 kb) and c-raf (3.8 kb) were expressed in all samples including normal lymphocytes without significant variation in the level of expression. C-fos (2.2 kb) was expressed in 15 samples and normal lymphocytes with a wide range in the level of expression. C-myb (3.7 kb) and c-fes (2.7 kb) were expressed at a low level in 6 and 10 samples, respectively, including normal lymphocytes. C-sis (4.0 kb) was not detected in any sample including normal lymphocytes.