P2Y receptors are pharmacologically distinguishable from one another by their differing selectivity for adenine and/or uracil nucleotides. The immortal human sweat gland cell line, NCL-SG3 has previously been shown to respond to purinoceptor stimulation (Wilson et al., 1994) making it an ideal model for the study of such receptors. Here we have further investigated the purinoceptor population within NCL-SG3 cells by cross-desensitisation of the [Ca²⁺]_i responses elicited by ATP, UTP, ADP and UDP.Changes in [Ca²⁺]_i were measured using a fura-2AM protocol as described in Lindsay et al., (2003). Non-cumulative concentration-response curves determined previously, demonstrated that after numerous passages the cells still responded to purinoceptor stimulation and exhibited a similar sensitivity to those of Wilson et al., (1994). Desensitisation experiments were performed by applying a maximal concentration of selected agonist for 10 min followed by the addition of a second agonist, in the continued presence of the first agonist. Values are presented as mean ± s.e.m. Statistical analyses were carried out using Student′s t-test, P≤0.05 considered significant. All nucleotides desensitised their own [Ca²⁺]_iown response. After ATP desensitisation, UTP elicited an increase in [Ca²⁺]_i of 0.81 ± 0.12 ratio units (n=5), while application of either ADP (n=4) or UDP (n=4) was ineffective. After UTP desensitisation, none of the three agonists could cause any further increase (n=5, all). After UDP desensitisation both ATP and UTP increased [Ca²⁺]_i by 0.72 ± 0.10 (n=4) and 0.79 ± 0.20 (n=4), respectively, however ADP was ineffective. After desensitisation with ADP, application of ATP, UTP and UDP produced an increase in [Ca²⁺]_i of 0.77 ± 0.13, 0.84 ± 0.18 and 0.34 ± 0.10 ratio units, respectively (n=4, all).Since UTP could fully desensitise the response to ATP it suggests that both agonists are acting on a P2Y₂ receptor, where ATP and UTP act equipotently. This is consistent with that found by Wilson et al., (1994). However, there was a component of the UTP response that could not be desensitised by ATP. This suggests the presence of P2Y₄ receptors where UTP acts potently, but ATP is ineffective. UDP could block the response to ADP indicating P2Y₆ receptors, that are activated by UDP but have some sensitivity to ADP (Communi et al., 1995). An unusual finding is that UTP blocked the response to ADP, yet according to current knowledge of P2Y classification, ADP is ineffective at receptors were UTP functions. Therefore, our results suggest a heterogeneous population of purinoceptors within NCL-SG3 cells.