The aim of this article was to investigate the effects of methanehydroxydiphosphonate (MHDP) and fluoride (F) separately and combined, on the demineralization process in enamel and in dentine under constant composition conditions. The demineralization was carried out in solutions containing 3 mM calcium, 3 mM phosphate, pH = 5.0, and either 6 muM MHDP, 12 muM F or 6 muM MHDP and 12 muM F. After demineralization periods (t) between 24 and 140 h, the lesion depth 1 and the mineral loss DELTAZ were measured by transverse microradiography of the enamel and dentine speciments. The amount of mineral lost during demineralization averaged over the lesion depth, R = DELTAZ/l, was calculated. R almost-equal-to 17 vol% for both enamel and dentine, both DELTAZ and 1 being greater for dentine than for enamel by approximately the same factor. The results show that under the same conditions dentine is attacked much more strongly than enamel. The lesion progress with time is quite different for the two tissues: in enamel the lesion depth progresses als l3 = alphat + beta, in dentine as l2 = alpha't + beta'. The slopes alpha and alpha' decrease in the order MHDP > F > MHDP + F. In enamel the combined inhibitor effect is only slightly larger than the effect of F alone; in dentine the inhibiting effects of F and MHDP are approximately additive. The inhibitor interactions can be described by the Langmuir adsorption theory. For the adsorption of F onto enamel the adsorption constant K(kin) was calculated to be 5.2 x 10(4) liters/mol, about an order of magnitude smaller than the corresponding value for hydroxyapatite. For adsorption of MHDP onto enamel, K(kin) was found to be 1.0 X 10(4) liters/mol, which is in the same range as the corresponding value for hydroxyapatite.