The structure and genetic variation of 18 wild and three domesticated populations of pepper (Capsicum annuum L.) from northwestern México were determined by isozymes and RAPDs. The isozyme analysis was based on 12 polymorphic loci from nine isozymes. All populations showed high genetic variation (A = 2.72, P = 90.8 %, He = 0.445 for wild populations; and A = 2.60, P = 84.6 %, He = 0.404, for domesticated populations). Most genetic variation occurred within rather than among populations. However, genetic differentiation was greater among domesticated (GST = 0.167) than among wild (GST = 0.056) populations. The RAPDs analysis performed with ten primers produced a total of 166 bands, all polymorphic in wild populations. Out of 126 bands, 125 were polymorphic in domesticated populations. Mean percentage of polymorphism was 34.2 and 34.7 % in wild and domesticated populations, respectively. Mean and total genetic diversity were 0.069 and 0.165 for wild populations, and 0.081 and 0.131 for domesticated populations. AMOVA showed that total genetic diversity was equally distributed among (50.0 and 48.9 %) and within (50.0 and 51.1 %) of both, wild and domesticated populations. Wild and domesticated populations were clearly differentiated in the UPGMA dendrogram built from isozymes data (average GD = 0.182), as well as by AMOVA (17.2 % of variance was among populations types, P ≤ 0.001). The considerable genetic distances found among varieties (average GD = 0.212 with isozimes) suggest that genetic changes associated with domestication have occurred in different directions.