Tritium-labeled eugenol was released from mixtures of zinc oxide eugenol (ZOE) into aqueous solution at rates which declined exponentially with time, and which were directly proportional to the liquid-powder ratio. The release pattern was consistent with a model of progressive hydrolysis of zinc eugenolate in a limited-thickness ZOE surface layer. Intervening dentin had a profound effect on this pattern of release. In human teeth in vitro containing ZOE as a base or temporary filling, peak eugenol release at the pulpal surface of dentin was of the order of a thousand-fold less than that at the salivary surface. In such teeth, eugenol reached concentrations in excess of 10(-2) M in dentin just beneath ZOE, and 10(-4) M or less adjacent to the pulp space. Both pulpal outflow and dentin concentrations of eugenol remained relatively constant for more than a week, unlike release into aqueous solution. While these data were derived from studies on human teeth in vitro, they give a strong indication of probable events in vivo, and appear to provide a basis for the explanation of the paradox of the therapeutic and toxic actions of ZOE.