The aim of the present study was to investigate the impact of a successful anti-myxosporean medication on the innate immune system of fish intensively cultured in the Mediterranean basin. For this purpose, juvenile and adult gilthead seabream (S. aurata L.) naturally infected with Polysporoplasma sparis in the kidney were used in a small-scale field trial. The infected fish were treated orally with the combination of salinomycin and amprolium, two drugs well known for their anti-coccidial effect in other animals. Drug efficacy and safety was evaluated in terms of changes observed in histopathology, mortality and P. sparis intensity and prevalence rate. Phagocytic functions of head-kidney leucocytes were also investigated at the end as well as one month post the medication. Salinomycin with amprolium exhibited a significant reduction in intensity and prevalence rate in both juvenile and adult fish, and no histopathological evidence for toxic side effects was observed. In addition, the successful treatment was closely correlated with a complete restoration of the diminished phagocytic ability and capacity as well as NO, and lysozyme secretion in a time dependent manner. This data suggests that salilomycin with amprolium can be an alternative treatment for myxosporean infections in warm-water fish, possibly exhibiting their action through the enhancement of host innate functions.Eukaryotic parasites are organisms with considerable genetic complexity that have evolved mechanisms to avoid elimination by the host's immune system. Fish immune reaction to parasites relies on the development of an efficient innate immune response, as adaptive immune mechanisms in poikilotherms manifest a rather slow onset and limited repertoire (1-2). Thus, macrophages and granulocytes have a prominent role in phagocytosis of pathogens as well as in the production ofreactive intermediates (3). Myxosporeans are the most common parasites affecting intensively cultivated fish in the Mediterranean basin, inducing a broad spectrum of unthreaded diseases determined by the parasite species, host sensitivity, and environmental and feeding conditions (4-8). They are often implicated in high mortality in sharpsnout and gilthead seabream with serious financial effects on the intensive fish farming industry (9-12). The continued and high mortality rate is in many ways associated with the absence ofan adequate treatment for warm water fish. Indeed, there are no licensed anti-parasitic compounds for Mediterranean species and all information is extrapolated from coldwater species, especially salmonids. This can cause problems as treatment conditions are different 0394-6320 (2005) This publication and/or article is for,individualC:~~Y~~1~ta~db~~yl~~I~;t'~~~h~r eproduced withoutwritten permission. from the copyright holder. Unauthorized reproduction mayresultin financial and otherpenalties