Maxillary canine-first premolar (Mx.C.P1) transposition, an uncommon dental anomaly involving positional interchange of the two teeth, was studied using a sample of 43 subjects with the abnormality. Data were recorded on sidedness, sex, race, tooth agenesis, and peg-shaped maxillary lateral incisors for each case. Mx.C.P1 transposition occurred bilaterally in nearly one-quarter of the sample and favored female expression (sex ratio, M1:F3.8) and left-side occurrence (61% of unilateral cases). Familial occurrence was noted, as was a predilection for white subjects. Tooth agenesis (excluding third molars) and/or peg-shaped maxillary lateral incisors accompanied Mx.C.P1 transposition in 49% (21) of the subjects, four to ten times the normal rate of occurrence. Data from this study and the analysis of previously published cases provided strong evidence that Mx.C.P1 transposition is a disturbance of tooth order and eruptive position resulting from genetic influences within a multifactorial inheritance model.