Gluconolactone was evaluated as an excipient for tablets prepared by direct compression using various drugs known to be difficult to compress. The physical properties of the tablets were evaluated after compression and after storage and were satisfactory. Comparative studies were conducted between gluconolactone and anhydrous lactose, a common direct compression diluent, for development of static charges during blending, flow, drug distribution, drug stratification, color distribution, compressibility, and preservation against mold growth. Gluconolactone possesses those properties necessary to produce high quality tablets by the direct compression process. Separate powdered mixtures of aspirin USP with gluconolactone, anhydrous lactose, spray-dried lactose, mannitol, and sorbitol were stored at various humidities and temperatures for specified periods and tested for the integrity of aspirin. Gluconolactone contributed least to the degradation of the drug as compared to other excipients studied. A preliminary in vivo study also was conducted on the bioavailability of aspirin from separate and similar mixtures with gluconolactone, anhydrous lactose, and starch. Gluconolactone did not show any inhibitory effect on aspirin absorption.