Apical nucleotides have been shown to inhibit Na⁺ transport in many absorptive epithelia, a response often attributed to P2Y₂ receptors which characteristically display equal sensitivity to ATP and UTP (Ramminger et al., 1999) and allow these nucleotides to increase [Ca²⁺]_i.We have now measured and [Ca²⁺]_i^ISC simultaneously and explored the effects of nucleotides upon the two parameters in H441 polarised cells. Apical ATP (Fig 1A) evoked a rapid transient in I_SC,followed by a larger sustained response that is accompanied by a comparable [Ca²⁺]_i response. In contrast, UTP (Fig 1B) evoked a transient increase in I_SC followed by a return to baseline, and was still accompanied by a large [Ca²⁺]_i signal. The different effects of ATP and UTP suggested the activation of separate receptor populations and not the proposed P2Y₂ subtype. Basolateral ATP and UTP evoked no discernible changes in I_SC or [Ca²⁺]_i.Apical Adenosine consistently evoked a monophasic increase in I_SC without an accompanying [Ca²⁺]_i response (Fig 1C), a smaller response (50% P<0.05 Students paired t test) was seen basolaterally. In the presence of the adenosine (A1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), UTP evoked [Ca²⁺]_i and I_SC signals were unaltered, however, the ATP evoked change in I_SC was reduced (P≤0.05) and not significantly different from that evoked by UTP; adenosine evoked no response. The sustained component of the I_SC response to ATP thus appears to be mediated by adenosine receptors, indicating that H441 cells do express only P2Y₂ receptors controlling both ion transport and [Ca²⁺]_i signalling in the apical membrane.