Erythrocyte acid phosphatase (ACP1) activity was determined in the absence of modulators and in the presence of either adenosine or inosine as modulators in 154 samples of red blood cells collected from adult donors. Adenosine and inosine showed modulating effects (activation), that were genotype dependent in the allele order pb less than pa less than pc; the activation by inosine was much higher than by adenosine. The modulating effect was dependent on adenosine deaminase (ADA) genotype: In carriers of ADA2 allele the activation with ACP1 phenotype A was lower and that with phenotypes CA and CB was higher than in ADA1/ADA1 subjects. In addition, the basic ACP1 activity (i.e., without modulators) also appeared to be dependent on ADA genotype: The lowest ACP1 activity was observed in A and BA subjects carrying the ADA2 allele. Since the deamination of adenosine to inosine associated with ADA2-1 phenotype is slower than that associated with ADA1, the interaction of ADA on ACP1 activity may in fact be explained by a lower intracellular concentration of inosine in ADA2 carriers and, therefore, by a lower modulating effect of this on acid phosphatase activity.