OBJECTIVE To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates. METHODS Randomized double blind study. METHODS Tertiary level Neonatal Intensive Care Unit. METHODS Eighteen preterms admitted during the period January 1994 to May 1994. METHODS The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required. METHODS Initial peak levels and steady state trough and peak levels in both groups. RESULTS Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity. CONCLUSIONS Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage.