We evaluated 124 patients for nephrotoxicity associated with gentamicin or amikacin therapy. The incidence of definite nephrotoxicity was 10.5% during therapy, with a mean increase in creatinine of 1.0 mg/100 ml (range, 0.5-3.6 mg/100 ml). Nephrotoxicity developed late in therapy (mean, day 10) and the creatinine continued to increase after cessation of therapy for as long as nine days. Age, initial creatinine, total dose and initial "peak" and "valley" levels did not correlate with nephrotoxicity. Nephrotoxicity developed in 8 of 97 patients treated for less than or equal to 11 days and 5 of 19 treated for greater than 11 days (chi square, p less than .01). "Peak" and "valley" levels rose significantly (t-test, p less than .05) during therapy and increased more in those with nephrotoxicity. A "peak" level of amikacin of greater than or equal to 38.5 micrometer/ml or of gentamicin of greater than or equal to 10 micrometer/ml or a rise in the "valley" levels of amikacin above 10 micrometer/ml was also associated with nephrotoxicity (chi square, p less than .025). These data help define the natural history and the host and drug factors that affect the development of gentamicin- and amikacin-induced nephrotoxicity.