Despite the many triumphs of comparative biology during the past few decades, the field has remained strangely divorced from evolutionary genetics. In particular, comparative methods have failed to incorporate multivariate process models of microevolution that include genetic constraint in the form of the G matrix. Here we explore the insights that might be gained by such an analysis. A neutral model of evolution by genetic drift that depends on effective population size and the G matrix predicts a probability distribution for divergence of population trait means on a phylogeny. Use of a maximum likelihood (ML) framework then allows us to compare independent direct estimates of G with the ML estimates based on the observed pattern of trait divergence among taxa. We assess the departure from neutrality, and thus the role of different types of selection and other forces, in a stepwise hypothesis-testing procedure based on parameters for the size, shape, and orientation of G. We illustrate our approach with a test case of data on vertebral number evolution in garter snakes.