Many shrimp diseases affect the normal histological architecture and functioning of the hepatopancreas and gut leading to disease conditions. In the present study, hepatopancreas and gut from a total of 60 farmed shrimp, Penaeus (Litopenaeus) vannamei from two different farming systems viz., inland saline (Haryana) and brackishwater (Maharashtra) were analysed histologically. No gross pathological changes, except for the retarded growth found in shrimp collected from Maharashtra, were observed in shrimp examined in the study. Histopathological changes observed in the hepatopancreas included tubular necrosis, sloughing of tubular epithelium, tubular atrophy, heavy haemocytic infiltration, abnormally enlarged haemal sinuses, encapsulation, nodule formation and melanisation. The hepatopancreas also revealed the presence of Enterocytozoon hepatopenaei (EHP) as deeply basophilic inclusion-like plasmodia contained within the vacuoles in tubule cytoplasm and aggregations of spores in the necrotized lumen (Fig. 1). Different stages of necrosis induced by the microsporidian were also identified. Forty-five animals collected during the study were also tested for pathogens/diseases such as EHP, WSSV, IHHNV, HPV, MBV, AHPND and NHP. PCR screening revealed higher prevalence of EHP (60%) in shrimp farmed in brackishwater system compared to the shrimp reared in inland saline water (20%). Histological analysis of hepatopancreas revealed aggregated transformed microvilli-like bodies characteristic of white faeces syndrome of shrimps (Fig. 2). However, no white faecal strands were observed in the field. Acute hepatopancreatic necrosis disease (AHPND)-like pathology marked by abnormally enlarged haemal sinuses and melanosis of necrotized tubules in the distal, medial as well as proximal part of hepatopancreas was also observed. Further, some of the shrimp samples revealed histopathological changes resembling necrotising hepatopancreatitis (NHP). However, PCR analysis did not reveal the presence of both VpAHPND and NHP bacteria in the samples. Co-infection with EHP and bacteria was also noticed in some of the animals in which necrotised hepatopancreas revealed EHP spores and bacterial cells (bacilli). Gut histology of the animals did not show any significant pathology in majority of cases. However, heavy degeneration of gut epithelium was noticed in shrimp which showed severe pathology in the hepatopancreas. PCR analysis did not show positive amplification for any of the viruses tested. The present study forms the first account of histological and PCR-based survey comparing shrimp farmed in two distinctly different culture systems of brackishwater and inland saline water.