The risk factors associated with gametocytaemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 767 children enrolled prospectively in 5 antimalarial drug trials between July 1996 and December 2002 in a hyperendemic area of southwestern Nigeria. The children were assigned to one of 6 treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only; amodiaquine (AQ) only; CQ combined with chlorpheniramine (CQCP); or PS combined with CQ (CQPS) or AQ (AQPS). At enrolment, 115 (15%) of 767 children were gametocyte carriers. During follow-up, 15(.)6% of all patients (i.e. 120 patients) developed patent gametocytaemia, which in 85% (102 patients) had developed by day 7 following treatment. In a multiple regression model, 4 factors were found to be independent risk factors for the presence of gametocytaemia at enrolment: male gender (adjusted odds ratio [AOR]=0(.)55, 95%) confidence interval [CI] 0(.)36-0(.)83, P=0(.)005), absence of fever (AOR=1(.)61, 95%, CI 1(.)05-2(.)5, P=0(.)03), duration of illness >3 days (AOR=1(.)57, 95% CI 1(.)0-2(.)4, P=0(.)047), and asexual parasite densities less than 5000/mul (AOR=0(.)42, 95% CI 0(.)24-0(.)73, P=0(.)002). The presence of patent gametocytaemia at enrolment (AOR=0(.)04, 95% CI 0(.)02-0(.)07, P<0(.)001) and recrudescence of asexual parasites within 14 days were associated with the presence of gametocytaemia 7 or 14 days after enrolment (AOR=0(.)5, 95% CI 0(.)3-0(.)8, P=0(.)007). Delay in the time taken to clear the initial parasitaemia (>2 days) was associated with increased risk of subsequent gametocyte carriage. These findings may have implications for malaria control efforts in sub-Saharan Africa where control of the disease depends almost entirely on chemotherapy.