AbstractThis article is concerned with the development of a model to maximize the overall yield of isolation of antibiotics recovered from fermented broths by the so‐called direct precipitation method. In this process, as in most antibiotics isolation processes, a second filtration of the semiexhaust mycellium from the first filtration, after slurrying it in water at the suitable pH, is required. The maximization of the overall yield of isolation implies the use of an optimal amount of water, measured as a volume to fermented broth mass ratio, which can be calculated by using the model derived here. The model also allows for the calculation of the partial and overall yields of the isolation process, and its validity is demonstrated by its ability to describe reasonably well the isolation data of two different tetracycline‐fermented broths produced according to two different technologies.The application of the model requires only the knowledge of easily obtainable fermented broth parameters and is illustrated for two different types of tetracycline‐fermented broths. Although the model had been derived for the optimization of the overall yield of isolation of antibiotics recovered by direct precipitation, it can easily be adapted to be used for the optimization of the overall yield of isolation of antibiotics recovered by other isolation processes. © 1993 John Wiley & Sons, Inc.