The aim of this article was to study interactions between different gel forming polymers and amphiphilic drugs and surfactants with the intention of finding interactions that can be used for designing controlled release formulations. The release from gels was measured by detecting the UV-absorbance of drugs released from 6 mL gel into 250 mL release medium in a dissolution bath. The rheological behavior of gels was characterized using a controlled rate rheometer. The diffusion coefficient of alprenolol was 6.3x 10(-6) cm(2)/s when formulated in a 1% poly(acrylic acid) gel (PAA) and 2.8 x 10(-6) cm(2)/s in a lipophilically modified gel (LM-PAA). The addition of alprenolol to 1% LM-PAA increased the elasticity, G', from 123 to 182 Pa. Increased gel strength was also observed for a number of other amphiphilic drugs. The addition of 1% Brij 58 to LM-PAA decreased the diffusion coefficient of alprenolol to 2.3 x 10-6 cm(2)/s. It was possible to sustain the release of charged drugs with high log P by adding surfactant micelles. However, the effect was small and only useful for drugs with adequate lipophilicity. The interaction between LM-PAA and amphiphilic drugs could be seen using rheology and was used for designing controlled release gel formulations. In this way surfactants can be avoided, thus decreasing toxicity problems. (C) Elsevier Science (USA).