Interactions among microorganisms found in coral mucus can be either symbiotic or competitive. It has been hypothesized that microbial communities found on the surface of coral play a role in coral holobiont defense, possibly through production of antimicrobial substances. Selected microorganisms isolated from the mucus layer of a number of coral species were grown using agar-plating techniques. Screening for antimicrobial substances was performed using overlay and drop techniques, employing several indicator microorganisms. Between 25% and 70% of cultivable mucus-associated bacteria from scleractinian corals demonstrated bioactivity. Higher percentages of activity were evident in mucus-associated cultivable bacteria from massive and solitary corals, as compared with bacteria from branching or soft corals. Isolates related to the genera Vibrio and Pseudoalteromonas demonstrated high activity against both Gram-positive and Gram-negative bacteria. Gram-positive bacteria (Bacillus, Planomicrobium) demonstrated lower levels of activity, primarily against other Gram-positive bacteria. In some cases, inhibitory effects were confined to the cell fraction, suggesting the involvement of a cell-bound molecule, sensitive to temperature and most likely proteinaceous in nature. These results demonstrate the existence of microorganisms with antimicrobial activity on the coral surface, possibly acting as a first line of defense to protect the coral host against pathogens.