A simulation method was developed for identifying populations with levels of human-caused mortality that could lead to depletion, taking into account the uncertainty of available information. A mortality limit (termed the Potential Biological Removal, PBR, under the U. S. Marine Mammal Protection Act) was calculated as the product of a minimum population estimate (NMIN), one-half of the maximum net productivity rate (RMAX), and a recovery factor (FR). Mortality limits were evaluated based on whether at least 95% of the simulated populations met two criteria: (1) that populations starting at the maximum net productivity level (MNPL) stayed there or above after 20 yr, and (2) that populations starting at 30% of carrying-capacity (K) recovered to at least MNPL after 100 yr. Simulations of populations that experienced mortality equal to the PBR indicated that using approximately the 20th percentile (the lower 60% log-normal confidence limit) of the abundance estimate for NMIN met the criteria for both cetaceans (assuming RMAX= 0.04) and pinnipeds (assuming RMAX= 0.12). Additional simulations that included plausible levels of bias in the available information indicated that using a value of 0.5 for FR would meet both criteria during these “bias trials.” It is concluded that any marine mammal population with an estimate of human-caused mortality that is greater than its PBR has a level of mortality that could lead to the depletion of the population. The simulation methods were also used to show how mortality limits could be calculated to meet conservation goals other than the U. S. goal of maintaining populations above MNPL.