In order to correlate hydrolysis rates under physiological conditions to differences in toxicity of trimethoxysilane, tetramethoxysilane, and methyltrimethoxysilane, the rates of hydrolysis of these compounds were studied in deionized water, sodium phosphate buffer solution at pH 7.4, and 10% rat serum in sodium phosphate buffer at 37.4 degrees C. A strong surface effect was observed on the hydrolysis rates of tetramethoxysilane in different reactors in the following decreasing order: quartz greater than soft glass (I) greater than stainless steel greater than Teflon greater than soft glass (II). By using the soft glass (II) reactor as the reaction vessel for hydrolysis experiments, trimethoxysilane and tetramethoxysilane were found to be very unstable in 0.15 M sodium phosphate buffer (pH 7.4) and 10% rat serum (0.15 M sodium phosphate buffer, pH 7.4) with similar rates of hydrolysis at greater than 3.0 min-1 (t 1/2 less than 0.23 min). Under similar conditions, however, the rate of hydrolysis for tetramethoxysilane in deionized water was measured to be considerably slower (k = 0.022 min-1; t 1/2 = 32 min) than that of trimethoxysilane (k greater than 8.1 min-1, t 1/2 less than 0.09 min). However, the rates of hydrolysis for methyltrimethoxysilane in water, sodium phosphate buffer at pH 7.4, and 10% rat serum were measured to be 0.03 min-1 (t 1/2 = 24 min), 0.10 min-1 (t 1/2 = 6.7 min), and 0.08 min-1 (t 1/2 = 8.6 min), respectively.