The hydrogel system of poly(methacrylic acid-co-N-vinyl pyrrolidone) P(MAA-co-NVP) was evaluated for use as an oral delivery system for growth hormone and salmon calcitonin. These proteins were selected because of their therapeutic importance and the insight provided by evaluating the delivery of a therapeutic agent with a high molecular weight (growth hormone) and a drug with a high isoelectric point (salmon calcitonin). Growth hormone loading and release studies were performed for both P(MAA-co-NVP) and P(MAA-g-poly(etaylene glycol)) (P(MAA-g-PEG)). Loading efficiencies for the respective systems were 50.9 +/- 1.8% and 57.8 +/- 4.1%; weight incorporation of the protein was determined to be 3.5 +/- 0.1% and 4.0 +/- 0.3%. At pH 7.4, growth hormone release of 90% occurred within 45 min for P(MAA-co-NVP) microparticles; 90% release was not achieved with P(MAA-g-PEG) microparticles until 180 min. At pH 1.2, no release occurred from P(MAA-co-NVP) microparticles, but 10% release occurred from P(MAA-g-PEG) microparticles. Salmon calcitonin loading and release were shown to be affected by the negative charges of deprotonated MAA; for system; with monomer molar feed ratios of 4:1, 1:1, and 1:4 MAA/NVP, loading efficiencies were determined to be 70.6 +/- 3.0%, 25.3 +/-1.2%, and 1.6 +/- 1.3%. Salmon calcitonin release was minimal from the copolymer with 4:1 MAA/NVP monomer feed at pH 7.4. The release improved when the pH was raised above physiological levels. These studies confirmed that P(MAA-co-NVP) was an effective oral delivery system for high molecular weight drugs, but improvements are needed before the system could be utilized for high isoelectric point therapeutic delivery.