Copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were prepared and used to fabricate a membrane-controlled reservoir-type controlled-release delivery system for chlorhexidine that should be suitable for intra-oral use. The reservoir of the system was prepared by softening an 80:20 mixture of chlorhexidine diacetate and 50:50 HEMA:MMA copolymer with methyl ethyl ketone (MEK), and pressing standard amounts of the resulting dough-like mixture into silicone rubber molds. A membrane was applied to the reservoirs by rotating them through a solution of 30:70 HEMA:MMA copolymer in MEK. The finished oval-shaped controlled-release pellets were approximately 4.7 mm wide, 3.3 mm high, and 7.4 mm long, and contained 45.0 +/- 3.7 mg of chlorhexidine diacetate. The mean in vitro release rate of chlorhexidine diacetate from the pellets into 37 degrees C water was 608 +/- 55 micrograms/24 h for days 2 through 11, and 389 +/- 50 micrograms/24 h for days 15 to 30 of the test period. The chlorhexidine released on day 30 was biologically active, as determined by a serial dilution assay against Streptococcus mutans. The extended release of biologically active chlorhexidine at a controlled rate from this system suggests that it is worthy of further evaluation for the intra-oral therapy of chlorhexidine-treatable oral infections in non-compliant and physically or mentally compromised individuals.