Thermally responsive hydrogels of N-isopropylacrylamide containing hydrophobic comonomers were synthesized by free radical polymerization in both toluene and water. Various hydrophobic monomers were used, i.e. methyl methacrylate, hexylacrylate, hexafluoroisopropylmethacrylate and hexafluorobutylmethacrylate. Also polymers containing hydrophilic methacrylic acid were synthesized. The swelling properties of the polymers, as well as polymers containing 30 wt% ephedrine or ibuprofen were investigated in pure water at temperatures from 20 degrees C to 46 degrees C. The swelling ratios of pure gels depended on the ratio of hydrophilic and hydrophobic structural units in the polymer, as well as on the network structures of the gels. The hydrophilic drug ephedrine was bound to polyacid gels causing deswelling of the gels due to electrostatic interactions. Ephedrine did not affect the swelling of the neural gels, however. Addition of hydrophobic ibuprofen made all the hydrogels collapse at room temperature no matter whether the gels were neutral or acidic. Interactions between spin probes, 4-benzoxy-2,2,6,6-tetramethylpiperidine-1-oxyl (BZONO) and 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (amino-TEMPO), and the polymer gels were studied using electron paramagnetic resonance spectroscopy. The hydrophobic probe BZONO resided in the gels below the lower critical solution temperature (LCST) due to hydrophobic interactions, but dissolved, at least partially, in the aqueous phase above the critical temperature. The distribution of BZONO between the gel and the aqueous phase depended on the hydrophobicity of the polymer. Also the hydrophilic probe amino-TEMPO was partially bound into the gels.