The levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), lactic dehydrogenase (LDH), and LDH isoenzyme patterns (LD1 to LD5) have been measured in lymphocyte extract from 28 patients with B-chronic lymphocytic leukemia (B-CLL). The activities of ADA, PNP, and LDH have been correlated with two morphological groups of B-CLL classified according to the percentage of large, nongranular, atypical lymphocytes (AL) in peripheral blood: "typical" B-CLL (less than 10% of AL, 21 cases) and "atypical" B-CLL (10-25% of AL, seven cases). Patients with atypical B-CLL had significantly (P less than 0.001) higher activities of ADA (0.46 +/- 0.17 U/10(9) cells), PNP (1.74 +/- 1.0 U/10(9) cells), and LDH (48.3 +/- 9.7 U/10(9) cells) than patients with typical B-CLL (ADA, 0.29 +/- 0.1 U/10(9) cells; PNP, 0.58 +/- 0.23 U/10(9) cells; and LDH, 29 +/- 10 U/10(9) cells). In addition, the "treatment-free period" was also significantly (P less than 0.025) shorter in the group of atypical B-CLL compared with the typical B-CLL group. No clear-cut statistical differences in lymphocyte surface markers or in several other prognostic factors between the two subgroups of B-CLL were found. The present study supports the idea that in B-CLL the simultaneous determination of ADA, PNP, and LDH might be helpful in better understanding the pathophysiology, prognosis, and natural history of the disease.