Failure to recognize infection caused by human immunodeficiency virus type 1 (HIV-1) group O variants has been described using both serological and genetic techniques. Moreover, the monitoring of response to antiretroviral therapy is difficult in persons carrying this infection since most currently available tests for quantifying viral load are not reliable for group O viruses. Considering the low level of divergence between the p24 proteins of group M and O viruses, we have examined whether the quantification of circulating p24 antigenaemia might be used as a surrogate marker of response to therapy in three subjects with HIV-1 group O infection treated with antiretroviral drugs. In summary, all three patients showed a significant decline in circulating plasma p24 antigenaemia, although only one achieved undetectable levels. The decline in p24 antigenaemia was parallel to an increase in the CD4 count and was associated with an improvement in clinical status.