Six morphine-dependent and three control macaques were infected with a mixture of SIV=SHIV. Half of the animals in the morphine group developed accelerated disease (rapid progressor) and died within 20 weeks postinfection. The evolution of the envelope gene in the brain of the rapid progressor and morphine-dependent group along with that in the control group was assessed. Six to 10 clones from the brain of each macaque were sequenced and were compared against each other as well as against a challenge virus. Analysis of the sequences revealed that the diversity and divergence of the clones were higher in the control group as compared to the morphine-dependent macaques, although this difference was not statistically significant.