Between January 1988 and December 1990, the National Blood Transfusion Service in Ghana tested the blood of 29,575 blood donors for HIV-1 antibodies to examine the significance in variations in monthly seropositivity. More than 90% of the blood donors were first-time donors. 20% were voluntary donors and the remaining donors were family donors. Over the study period, the Service used 4 different test kits: Wellcome ELISA (January 1988-November 1989), hemagglutination method ( December 1989-February 1990), Wellcome recombinant ELISA (February-October 1990), Elavia ELISA (November-December 1990). It screened 9739, 9279, and 10,557 blood donors in 1988, 1989, and 1990, respectively. The monthly HIV-1 seropositivity rates were 0.9-4.4%, 1.4-10.1%, and 0.2-6.9% in 1988, 1989, and 1990, respectively. When the Service used just Wellcome recombinant ELISA (April-October 1990), the range was only 0.2-2%. Differences in the standard errors between the HIV-1 seropositivity rate for that month and that of the rest of the year were significant, especially in the 7-month period in which the Service used just the recombinant ELISA method. Contributing factors to the wide deviations included changes in testing kits, inability to repeat tests on all positive samples, and many first-time donors.