Microsphere size is a primary determinant of solute release velocity. We present here a rational way for producing PLGA microspheres with different and controlled sizes. The following process variables were studied: Stirring velocity during the second emulsion step, dispersed and continuous phases volume ratio, and poly(vinyl alcohol) concentration in the continuous phase. A full factorial experimental design 2(3) with triplicate at the central point was used to determine the influence of variables on PLGA microsphere mean size. The stirring velocity and poly(vinyl alcohol) concentration were the main variables at 0.95 significance level. An influence of PVA and stirring velocity on microspheres size is observed, there is no correlation for DP/CP volume ratio on size of microspheres. By combining the two variables--the stirring velocity and poly(vinyl alcohol) concentration, the surface response was analyzed. The increase of poly(vinyl alcohol) concentration with concomitant increase on stirring velocity produced microspheres with the lower sized. In contrast the lower poly(vinyl alcohol) concentration and the lower stirring velocity used produced the higher microspheres sized. Uniformly spherical and smooth microspheres (4-15 microm of diameter) were obtained. No significant difference was observed on Ponca S loading within the experimental region. Our results open the possibility of formulating PLGA microspheres with custom sizes performing a minimum of experiments as required for specific applications.