Clinical evidence indicated that effective substitution of azithromycin capsule with a tablet dosage form should be based on evidence of providing equivalent in vivo AUC/MIC ratio at the site of infection. This study was designed to compare the bioavailability of a generic azithromycin capsule and assess its bioequivalence with Zithromax tablets marketed in Jamaica. Healthy adult volunteers were recruited following official institutional protocols and randomly assigned to pre- and post wash-over periods of the tests. Sampled plasma levels were analyzed using validated HPLC method. Drug’s bio-disposition mechanism in the subjects was determined using the Gastroplus pharmacokinetics software. Model evaluation with Akaike Information Criterion (AIC) and Schwarz Criterion (SC) indicated one-compartment and two-compartment open models as the best for modeling azithromycin bioavailability from tablets and capsules respectively. However, statistical analysis showed no statistical significance between the respective bioavailability parameters of capsules and tablets, and they fell generally within the US FDA acceptance range of -20% to +25 % of reference product. Azithromycin release from tablets fits one-compartment while from capsules fits the two-compartment open models respectively. Azithromycin capsules were bioequivalent to its proprietary tablets and can be substituted in black male subjects if administered at least two hours before meals.