We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different groups but in type 1, IL-8mRNA was increased compared with type 3 (P = 0·001) and control (P = 0·001). In type 1, IL-10 by PBMCs had a low mean value (14·5±1·6) compared with (16·7±1·5) type 3 and (16±2·3) in controls (P<0·001 and P<0·001, respectively). In Blastocystis sp. type 1, low IL-10 was associated with lymphocyte and plasma cell infiltration (P = 0·015 and P = 0·002, respectively). In Blastocystis sp. type 1 and type 3, IL-12 was associated with goblet cell depletion 23 (85%) (P<0·001) and 8 (29%) (P = 0·037), respectively. In Blastocystis sp. type 1, low IL-10 was associated with a proinflammatory response characterized by IL-8.