Lines of mice which have been genetically differentiated in litter size at birth and 6-week body weight by single-trait or index selection were randomly assigned to be reared in postnatal litter sizes (PLS) of N8, N12 or N16. The lines were selected as follows: large litter size (L+), large 6-week body weight (W+), selection index to decrease litter size and increase 6-week body weight (L-W+), selection index to increase litter size and decrease 6-week weight (L+W-) and random selection (K). Line and PLS differences in female body weight at weaning and 6 weeks were significant (P less than .05), with W+ greater than L+ greater than L-W+ greater than K greater than L+W- and N8 greater than N12 greaater than N16. Although there was a significant interaction between line and PLS, ranking of the lines was the same at each PLS. Females of each line by PLS group were exposed to males of the same group. Line and PLS differences (P less than .05) in female body weight at copulatory plug, adjusted for age, exhibited the same rankings as the earlier weights. Litter size at birth (dead plus alive), number born alive and number born alive per female exposed each revealed similar differences (P less than .05) in the ranking of lines and PLS. No significant interactions were found. Means for litter size were as follows for each line: L+ (17.4) greater than [W+ (14.1), L+W- (14.3)] greater than K (12.0) greater than L-W+ (10.8), and for each PLS: [N8 (14.0), N12 (13.9)] greater than N16 (13.2). The decline in litter size as PLS increased did not differ significantly from linearity. Adjusting litter size for body weight at copulatory plug eliminated the significant effect of PLS [N8 (13.9), N12 (13.7), N16 (13.4)]. The established genetic differences in litter size among lines due to selection were considerably larger than the maternal environmental effect due to postnatal litter size. Because of the negligible interaction between line and PLS, valid inferences concerning genetic differences among lines in litter size may be made at any postnatal litter size between eight and 16.