We have established the association between parasite burden and localized immune response in patients with cutaneous leishmaniasis (CL) caused by Leishmania tropica. Real-time PCR was used to measure parasitic load in tissue lesions of CL patients at the pretreatment (n=26) and at the post-treatment stage (n=10). Leishmania tropica was detected in all CL lesions with a mean value of 118 357 parasites g(-1) of dermal tissue. Following treatment, only one out of 10 patients showed residual parasites (100 parasites g(-1) tissue). Parasite load was high (mean, 306 000 parasites g(-1) tissue) in acute infections (early lesions) and low (mean, 1081 parasites g(-1) tissue) in chronic infections (late lesions). Intralesional transcripts of interferon-gamma, tumour necrosis factor-alpha, interleukin-1beta (IL-1beta), IL-8, IL-10 and IL-4 were investigated in early lesions (<or=2 months, n=14) and late lesions (>2 months, n=15) by reverse transcriptase-PCR, where IL-4 was found to be significantly upregulated in early lesions (P<0.02). Further, the levels of parasite burden and IL-4 were distinctly correlated in various clinical forms of CL. Other cytokines were at comparable levels in early/late lesions and in different clinical forms. Upregulation of IL-4 was correlated with a higher parasite burden in early lesions of CL, which may be involved in the pathogenesis of CL by inhibiting a protective immune response.