Slow release formulations (SRFs) are developed on the basis that the response elicited by a drug is closely related to changes in its plasma concentrations. As a consequence, the drug in the SRF is considered bioequivalent to the same drug administered in a conventional or immediate release formulation (IRF). The available literature suggest that for drugs eliciting a simple response, i.e. theophylline, the response is not affected by the rate of input of drug into the systemic circulation. Therefore, the pharmacodynamics are closely related to the pharmacokinetics of the drug, which are independent of formulation. In this case, SRFs and IRFs are truly bioequivalent. The pharmacological effect of some drugs, e.g. nifedipine, prazosin, furosemide (frusemide), etc., triggers compensatory homeostatic mechanisms. Therefore, the measured effect may not directly relate to the plasma drug concentration. Furthermore, the characteristics of the response will be modulated by the rate of input of the drug, i.e. drugs in SRF will elicit a greater response because a slow input triggers fewer homeostatic reactions. As a consequence, for drugs that trigger homeostatic reactions, a drug released from an SRF may not be bioequivalent to the same drug released from an IRF. Finally, when tolerance to an effect develops, a drug administered as an SRF will elicit a smaller effect than when administered as an IRF. Therefore, even if the different formulations of a drug were bioequivalent on the basis of pharmacokinetic parameters, they would not be equivalent on the basis of pharmacodynamic factors.(ABSTRACT TRUNCATED AT 250 WORDS)