This study investigated the effects of computer assisted instruction (CAI) on secondary school students' performance in biology. Also, the influence of gender on the performance of students exposed to CAI in individualised or cooperative learning settings package was examined. The research was a quasi experimental involving a 3 x 2 factorial design. The sample for the study comprised 120 first year senior secondary school students (SSS I) sampled from three private secondary schools, in Oyo State, Nigeria. The students' pre-test and post test scores were subjected to Analysis of Covariance (ANCOVA). The findings of the study showed that the performance of students exposed to CAI either individually or cooperatively were better than their counterparts exposed to the conventional classroom instruction. However, no significant difference existed in the performance of male and female students exposed to CAI in either individual or cooperative settings. Based on the research findings recommendations were made on the need to develop relevant CAI packages for teaching biology in Nigerian secondary schools. (Contains 4 tables.)