In contrast to the attention given to the relative levels of achievement of boys and girls in mathematics, the question of whether there are sex differences in the solution of chemistry questions has not attracted much attention. This study compares the performance of boys and girls in the Australian National Chemistry Quiz (Chem Quiz), a multiple‐choice test conducted by the Royal Australian Chemical Institute. The analyses were based on results from 27,000 students in Years 11 and 12 and 16,000 students in Year 10 who completed the Chem Quiz in 1991. Although some questions in the Chem Quiz were solved equally well by boys and girls, on many questions boys outperformed girls. The extreme case was a question answered correctly by 67% of Year 10 boys in contrast to 48% of Year 10 girls. Several reasons why boys and girls might differ in the rates they solve at least some chemistry questions are discussed, and directions for identifying the nature, extent, and basis for sex differences are outlined.