In a British National Lymphoma Investigation (BNLI) trial, patients with advanced Hodgkin's disease (stages IB, IIB, III, and IV) were randomized between initial treatment with a LOPP alternating with EVAP regimen and a LOPP/EVA hybrid regimen. The two regimens contained identical drug dosages and varied only in their scheduling. The complete remission (CR) rate in the hybrid regimen was significantly less than that in the alternating regimen, and the trial was terminated after approximately 18 months since there appeared to be no chance of the hybrid regimen ever proving superior to the alternating regimen. A total of 160 patients were entered into the trial before recruitment was terminated, 86 being randomized to the alternating regimen and 83 to the hybrid regimen. The CR rates for the alternating and hybrid arms were 65% and 40%, respectively (p < 0.002). The CR relapse-free survivals at 2 years in these two arms were 85% and 79%, respectively (p = 0.7); the overall disease-free survivals at 2 years were 57% and 32%; and the overall survivals at 2 years were 88% and 78% (p = 0.5). This trial emphasizes the impact of drug scheduling, which should be taken into account in the design of future hybrid regimens.