We investigated inbreeding in 3 outport Newfoundland study areas in which persistent genetic isolation was demonstrated previously. The inbreeding coefficient of every person born in each area was calculated from reconstructed pedigree data. The average inbreeding coefficient for persons born between 1960 and 1979 is 0.0032 in Trepassey Parish (southern Avalon Peninsula), 0.0171 for a group of communities on the west coast of the Great Northern Peninsula, and 0.0007 for southeastern Labrador. Average inbreeding of these populations was higher earlier in this century. Averages are high compared to those reported for other populations, consistent with genetic isolation. Coefficients of kinship were calculated for large samples of pairs of births in each study area, and frequency distributions of inbreeding coefficients compared with frequency distributions of kinship coefficients, to evaluate random and nonrandom mating with respect to consanguinity. These comparisons show that matings between unrelated individuals are more frequent than expected, that matings between first cousins are not strongly avoided in 2 of the 3 study areas, that matings between first cousins once removed are favored, and that matings between distantly related individuals are becoming more frequent. To gain an impression of the potential contribution of inbreeding to the prevalence of recessive disease, we calculated indirect estimates of the expected excess of prereproductive mortality due to inbreeding. These estimates are 15% for Trepassey Parish, 49% for the West Coast study area, and 2% for southeastern Labrador. It is unlikely that genetic isolation of outport Newfoundland populations will decrease. Elevated prevalences of recessive disease, due primarily to matings between persons unaware of their distant consanguinity, therefore require consideration in health care planning in Newfoundland.