The volume phase transition of nonionic hydrogels was controlled with a very small amount of variation (pinpoint variation) of the side chains far from the main chain. The copolymer hydrogels poly(methacryloyl-alanine methyl ester-co-methacryloyl-alanine ethyl ester) [poly(MA-Ala-OMe-co-MA-Ala-OEt)] and poly(methacryloyl-alanine alkylamide-co-methacryloyl-alanine ethyl ester) [poly(MA-Ala-NR2-co-MA-Ala-OEt)] were studied to investigate how pinpoint variation controls the volume phase transition. All copolymer hydrogels showed a volume phase transition from a swollen phase to a collapsed phase at a definite MA-Ala-OEt content at a specific temperature. The MA-Ala-OEt content at the midpoint of the transition linearly decreased with elevation of the temperature, and the decrease was larger for poly(MA-Ala-OMe-co-MA-Ala-OEt) than for poly(MA-Ala-NR2-co-MA-Ala-OEt). These results suggest that the association of the side chains controlling the swelling character of the hydrogels depends on the interacting ester-ester or ester-amide groups, and the former is larger than the latter. (C) 2000 John Wiley & Sons, Inc.