Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection are inconsistent. We assessed complete blood counts and selected serum chemistry measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II-seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic regression were used to adjust for potential confounding variables including age, gender, race/ethnicity, education level, blood center, and injection drug use. Compared with seronegative donors, absolute lymphocyte counts were 6% and 10% higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001) donors, respectively. HTLV-I- and HTLV-II-seropositive donors had, on average, 17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I-infected donors also had an average of 30 fewer eosinophils/μl (p = .003) and a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil counts may be related to the increased susceptibility of HTLV-I-infected subjects to parasitic diseases.